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My overall field of interest is developmental nephrology with extensive knowledge of renal morphogenesis as well as neonatal renal physiology and pathophysiology. My research effort has focused on advancing our understanding of the vaso-active factors that control neonatal renal blood flow and that facilitate the transition of renal hemodynamics from newborn to adult capability. The specific objective of these studies has been to examine the regulatory mechanisms producing the enhanced role of Nitric Oxide, NO, identified in preliminary experiments as a critical vasodilator in the neonatal kidney and during postnatal renal development. Utilizing novel experimental techniques, our NIH sponsored studies determined that the enhanced role for NO in the immature kidney is due to the increased expression and function of two isoforms of Nitric Oxide Synthase, nNOS, neuronal NOS, and eNOS, endothelial NOS, and that this condition is mechanistically regulated by Angiotensin II, AII. The studies also show that the two NOS isoforms exhibit differential expression and functional properties that are unique to the neonatal renal resistance microvasculature. Further, an important discovery is that nNOS is the predominate vasoactive NOS isoform in the newborn kidney, in contradistinction to the major role of eNOS in adult renal hemodynamics. The expression and function of nNOS is regulated specifically by AII via its AT1 receptor. Our work in characterizing this regulatory interplay between nNOS and AII from birth to renal maturity has significant ramifications in the clinical setting, particularly in the condition of acute renal failure of the newborn. Additionally, the transition from nNOS vasoactivity in the newborn to eNOS in the mature adult kidney has implications for the physiologic requirement to acquire fully capable adult renal function. Failure to successfully make this transition could impact the development of adult diseases, such as salt-dependent hypertension.

I am currently the NIH Mentor for the K08 award of Dr. Liwei Huang, K08 DK093625-01A1. "Wnt5a and Planar Cell Polarity in Kidney Development and Renal Cyst Formation”. The major goals of this project are to investigate the role of Wnt5a and planar cell polarity in kidney development and renal cyst formation.